Abstract

Background

DNA methylation is a contributing factor to both rare and common human diseases, and
plays a major role in development and gene silencing. While the variation of DNA methylation
among individuals has been partially characterized, the degree to which methylation
patterns are preserved across generations is still poorly understood. To determine
the extent of methylation differences between two generations of mice we examined
DNA methylation patterns in the livers of eight parental and F1 mice from C57BL/6J
and DBA/2J mouse strains using bisulfite sequencing.

Results

We find a large proportion of reproducible methylation differences between C57BL/6J
and DBA/2J chromosomes in CpGs, which are highly heritable between parent and F1 mice.
We also find sex differences in methylation levels in 396 genes, and 11% of these
are differentially expressed between females and males. Using a recently developed
approach to identify allelically methylated regions independently of genotypic differences,
we identify 112 novel putative imprinted genes and microRNAs, and validate imprinting
at the RNA level in 10 of these genes.

Conclusions

The majority of DNA methylation differences among individuals are associated with
genetic differences, and a much smaller proportion of these epigenetic differences
are due to sex, imprinting or stochastic intergenerational effects. Epigenetic differences
can be a determining factor in heritable traits and should be considered in association
studies for molecular and clinical traits, as we observed that methylation differences
in the mouse model are highly heritable and can have functional consequences on molecular
traits such as gene expression.